His next defense would change both his life and the face of boxing: On November 13, 1982, a 21-year-old Mancini met 23-year-old South Korean challenger Duk Koo Kim. Kim had to go through the process of losing several pounds immediately before the fight to make the weight. The title bout, at Caesars Palace in Las Vegas, was televised live at 1pm PST on CBS Sports, and by fight time Kim was spent. It was, according to many observers, a fight filled with action, but Mancini had an easy time hitting Kim during the 14 rounds the fight lasted. Kim suffered brain injuries that led to his death five days later. The week after his death, the cover of Sports Illustrated magazine showed Mancini and Kim battling, under the title "Tragedy In The Ring".

Mancini went to the funeral in South Korea, but he fell into a deep depression afterwards. He has said that the hardest moments came when people approached him and asked if he was the boxer who "killed" Duk Koo Kim. Mancini went through a period of reflection, as he blamed himself for Kim's death. In addition, Kim's mother committed suicide four months after the fight, as did the bout's referee, Richard Green, in July 1983.

As a result of this bout, the WBC took steps to shorten its title bouts to a maximum of 12 rounds. The WBA and WBO followed in 1988, and the IBF in 1989.